The purpose of this study is to evaluate the safety and tolerability of an experimental HIV vaccine. The vaccine will be given with or without IL-12 DNA adjuvant (at three escalating doses of 100, 500, and 1,500 mcg respectively), a substance that helps the body respond to a vaccine. This study will also determine the safety and tolerability of an experimental HIV vaccine boosted with two adjuvants.

A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of an HIV-1 Gag DNA Vaccine With or Without IL-12 DNA Adjuvant, Boosted With Homologous Plasmids in Healthy, HIV-1 Uninfected Adult Participants

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Safety, as judged by local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse and serious experiences [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Immunogenicity, as judged by HIV-specific cellular responses assessed by interferon-gamma ELISpot assays and by intracellular cytokine staining (ICS) [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Biological: Sodium chloride injection (0.9%)

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Biological: HIV-1 gag DNA plus IL-12 DNA adjuvant

Injection IL-12 DNA adjuvant intramuscularly into the deltoid

Biological: Sodium chloride injection (0.9%)

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Biological: HIV-1 gag DNA plus IL-12 DNA adjuvant

Injection IL-12 DNA adjuvant intramuscularly into the deltoid

Biological: Sodium chloride injection (0.9%)

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Biological: HIV-1 gag DNA plus IL-12 DNA adjuvant

Injection IL-12 DNA adjuvant intramuscularly into the deltoid

Biological: Sodium chloride injection (0.9%)

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

Experimental: 5

HIV gag DNA vaccine or placebo on Days 0, 28, 84, 168, and 273

Biological: HIV-1 gag DNA

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Biological: Sodium chloride injection (0.9%)

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Biological: HIV-1 gag DNA plus IL-12 DNA adjuvant

Injection IL-12 DNA adjuvant intramuscularly into the deltoid

Biological: CTL MEP/RC529-SE/GM-CSF (CTL MEP vaccine)

A 1 mL intramuscular injection in the deltoid

Biological: Sodium chloride injection (0.9%)

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

A 0.75 mL intramuscular injection of HIV gag DNA vaccine into the deltoid

Biological: Sodium chloride injection (0.9%)

All placebo groups will receive an intramuscular injection of sodium chloride (0.9%) in the deltoid.

Group 1 will receive a 0.75 mL injection on Days 0, 28, and 84. Group 2 will receive a 0.8 mL injection on Days 0, 28, and 84. Group 3 will receive a 1.0 mL injection on Days 0, 28, and 84. Group 4 will receive a 1.5 mL injection on Days 0, 28, and 84. Group 5 will receive a 0.75 mL injection on Days 0, 28, 84, 168, and 273. Group 6 will receive a 1.5 mL injection on Days 0, 28, 84, 168, and 273. Group 7 will receive a 1.5 mL injection on Days 0, 28, and 84 and a 1 mL injection into the deltoid on Days 168 and 273.

Detailed Description:

The HIV epidemic is a major global health challenge, causing tremendous human suffering and economic loss throughout the world. The need for a safe, effective, and affordable HIV preventive vaccine is critical. This study will determine the safety and immunogenicity of an experimental HIV vaccine, HIV-1 gag DNA, given with or without an IL-12 adjuvant and boosted HIV-1 gag DNA with or without IL-12 DNA adjuvant.

This study will comprise two parts (Parts A and B). Part A will last 9 months and Part B, 15 months. Part A will consist of 48 participants enrolled in 4 groups. Group 1 participants will be randomly assigned to receive the gag DNA vaccine or placebo. Participants in Groups 2, 3, and 4 will be randomly assigned to receive the gag DNA vaccine and either 100 mcg, 500 mcg, or 1,500 mcg IL-12 DNA or placebo. Vaccinations for Groups 1 through 4 will be given intramuscularly and will occur at study entry and at Months 1 and 3.

Part B will consist of 96 participants, enrolled in 3 groups. Participants in Part B will receive their first vaccination 2 weeks after Part A participants receive their second vaccination. Group 5 participants will receive either the HIV-1 gag DNA vaccine or placebo. Group 6 participants will receive either the HIV-1 gag DNA vaccine plus IL-12 DNA or placebo. Vaccinations for Groups 5 and 6 will occur at study entry and at Months 1, 3, 6, and 9. Group 7 participants will receive either the gag DNA vaccine plus IL-12 DNA or placebo at study entry and at Months 1 and 3. Throughout the study, blood and urine collections will occur, physical exams will be conducted, HIV testing and counseling will be offered, and interviews and questionnaires will be completed.

Eligibility

Ages Eligible for Study:

18 Years to 50 Years (Adult)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

HIV uninfected

Access to a participating HIV Vaccine Trials Unit (HVTU)

Willing to receive HIV test results

Willing and able to comply with all study requirements

In good general health

Willing to use acceptable methods of contraception for at least 21 days prior to study entry and until the last study visit. More information about this criterion can be found in the protocol.

Thyroid disease or surgical removal of the thyroid requiring medication during the 12 months prior to study entry

Accumulation of fluid in the blood vessels (angioedema) within 3 years prior to study entry, with episodes requiring medication in the 2 years prior to study entry

Hypertension that is not well controlled by medication OR blood pressure of 150/100 or higher at study entry

Body mass index (BMI) of 40 or greater OR BMI of 35 or greater, if certain criteria are met. More information about these criteria can be found in the protocol.

Bleeding disorder

Cancer. Participants with surgically removed cancer that, in the opinion of the investigator, is unlikely to recur are not excluded.

Absence of the spleen

Plans to become pregnant during the study

Pregnancy or breastfeeding

Exclusion Criterion for Participants in Part B:

Allergies to yeast-derived products

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00111605